Hypertension mediated by tacrolimus is largely caused by activation of the renal sodium chloride cotransporter (NCC), say researchers. In wild-type mice, tacrolimus caused salt-sensitive hypertension and increased levels of phosphorylated NCC, whereas in NCC-knockout mice, it did not affect blood pressure. The hypertensive response to tacrolimus was increased In NCC-overexpressing mice. NCC-blocking drugs reversed tacrolimus-induced hypertension in mice and increased fractional chloride excretion in human renal transplant recipients.